These studies focused on the properties of the two neuronal pterin- dependent aromatic amino acid hydroxylases, tyrosine and tryptophan hydroxylase, which mediate the biosynthesis of catecholamines and serotonin, respectively. Deletions within the N-terminus of tyrosine hydroxylase caused a marked increase in activity and a decrease in the sensitivity to catecholamine inhibition, an indication that the N-terminus imposes a constraint on the catalytic center and probably facilitates the binding of inhibitory catecholamines. We have successfully cloned and expressed in E. coli, tryptophan hydroxylase derived both from rabbit and human brain. This will facilitate the purification of large amounts of enzyme that can then be used for extensive structural and biochemical characterization. Preliminary results suggest that BH4 the obligatory cofactor for the synthesis of dopamine, also regulates its release. The mechanism underlying this effect is currently under investigation.